Experimental determination and mathematical model of the transient incorporation of cholesterol in the arterial wall.
Experimental data of the radial incorporation of labeled cholesterol [14C-4] into the artery wall is regressed against a mathematical model that predicts macromolecular transport in this biological system. Data is obtained using excised canine carotid arteries that are perfused in vitro under pulsatile hemodynamic conditions for 2 hr. Vessels are exposed to either normotensive hemodynamics, hypertensive hemodynamics, or simulations in which the rate of flow or vessel compliance is deliberately altered. Several arteries are studied under normotensive conditions following balloon catheter deendothelialization. Transmural concentration profiles of [14C-4] activity are determined by microcryotomy of longitudinal sections of perfused vessels. Nonlinear Marquardt regression on 12 experimental cases yields parameter estimates of effective diffusivity, D and solute filtration velocity, V. Results of this experimental investigation support our hypothesis that hemodynamics and the endothelial lining influence wall flux in intact vessels. Exposure to altered (vs normotensive) hemodynamics is associated with increased incorporation of labeled cholesterol. A similar observation is made for deendothelialized vessels (e.g. a greater accumulation of label and a rise in convective flux). Based upon our companion measurements of vessel wall forces and endothelial cellular morphology accompanying hemodynamic simulations, we suggest that hemodynamically induced alterations to endothelial structures lead to the increased permeability, convection and incorporation that we observe in this work.
Neumann
S J
SJ
Department of Surgery, University of Pittsburgh School of Medicine, PA 15261.
Berceli
S A
SA
Sevick
E M
EM
Lincoff
A M
AM
Warty
V S
VS
Brant
A M
AM
Herman
I M
IM
Borovetz
H S
HS
D000818:Animals; D001158:Arteries / Q000378:metabolism*; D001161:Arteriosclerosis / Q000209:etiology; D001693:Biological Transport, Active; D002784:Cholesterol / Q000378:metabolism*; D004285:Dogs; D006439:Hemodynamics; D066298:In Vitro Techniques; D008954:Models, Biological
D002784:Cholesterol